Barbituric acid compounds of i-phe



Patented Sept. 17, 1935 BARBITURIC ACID was PATENT OFlE COMPOUNDS 0F 1-PHE- NlYL -2,3- DHIETHYL -4- ISOPROPYL-5-PY- RAZOLONE Otto Schnider,

Basel, Switzerland, assignor to Hoffmann-La Roche Inc., Nutley, N. J., a corporation of New Jersey N0 Drawing. Application December 6, 1934, Serial No. 756,330. In Germany January 8, 1934 2 Claims.

It is known that l-phenyl-2,3-dimethyl-5- pyrazolone and also 1-phenyl-2,3-dimethyl4-dimethylamino-5 -pyrazolone form compounds with dialkyland arylalkyl-barbituric acids (German ;Patent No. 479,669 and United States Patents Nos.

(R being a saturated or unsaturated alkyl, R an aryl or a saturated alkyl group). They are very easily prepared in view of the great facility with which the components unite. 1phenyl-2,3,-dimethyll-isopropyl-E-pyrazolone is melted together with an equimolecular quantity of a dialkylor arylalkyl-barbituric acid or the starting materials are allowed to react together in the presence of a solvent or a diluent. The combination of 1-phenyl-2,3-dimethyl-4-isopropyl-5-pyrazolone and the dialkylor arylalkyl-barbituric acids always takes place in equimolecular proportions, even if larger quantities, for instance 2 molecules, of the one or the other component are present.

The new and very stable compounds are obtained in well-shaped crystals; by treatment with a solvent they cannot be split into their components. They are easily soluble in organic solvents, difficultly soluble in water. The new compounds are to be used as medicines, as they possess analgesic and antipyretic and likewise soporific properties. In these compounds the antipyretic and analgesic action of the pyrazolone component is considerably stronger, Whereas the soporific action of the dialkyland arylalkylbarbituric acids remains almost unaltered.

Ezmmple 1 105 parts by weight of isopropyl-allyl-barbituric acid are dissolved while heating in 600 parts by weight of benzene and 115 parts by Weight of 1-phenyl-2,3-dimethyl-l-isopropyl-5- pyrazolone in 200 parts by weight of benzene, the solutions are united while still warm, and petroleum ether is added until a turbidity begins to appear. On cooling 200 parts by weight of the new compound are precipitated in fine colorless needles melting at 128 C. Neither the melting point nor the aspect of the compound are changed 10 by recrystallization from dilute alcohol or dilute acetone. The remainder of the compound may be obtained by evaporating the mother liquor.

Example 2 weight of 1-phenyl-2,3-dimethyl-4-isopropyl-5- pyrazolone in 300 parts by weight of acetone is 20 added. On cooling the new compound is precipitated in fine needles melting at 161 C. They are easily soluble in organic solvents, difficultly soluble in water. The first crystallization yields about 400 parts by weight. The remainder may 25 be precipitated from the mother liquor by the addition of water.

Example 3 290 parts by weight of C,C-,B-bromo-allyl-iso- 30 propyl-barbituric acid are dissolved in 900 parts by Weight of alcohol. A solution of 230 parts by Weight of l-phenyl-2,3-dimethyl-4-isopropyl-5-pyrazolone in 500 parts by Weight of 90% alcohol is prepared and the solutions are 35 united while warm. From the clear colorless mixture 480 parts by weight of the new compound are precipitated while cooling. The colorless needles melt at 134-135 C. By adding a little water to the mother liquor a further 30 parts by 40 weight may be obtained which, on being recrystallized from dilute alcohol, likewise show a melting point of 134-135 C.

Example 4 45 parts by Weight of isopropyl-allyl-barbituric acid are well ground together with parts by weight of 1-phenyl-2,3-dimethyl-4-isopropyl-S-pyrazolone. The mixture melts indefinitely at 92-l00 C. It is suspended in 4000 50 parts by weight of water and stirred at 50*55 C. After 2 hours the compound shows a sharp melting point of 127 C. After recrystallization from dilute alcohol the melting point rises to 128 C. 55

Example 5 230 parts by weight of 1-phenyl-2,3-dimethyl- 4-isopropyl-5-pyrazolone are dissolved in 600 parts by weight of methanol while heating. A Warm solution of 184 parts by weight of diethyl-barbituric acid in 1400 parts by weight of 50% methanol is added. On cooling 360 parts by Weight of the new compound are precipitated in crystals melting at 138-139 C. The remainder is obtained from the mother liquor by precipitating with water.

Example 6 210 parts by weight of isopropyl-allyl-barbituric acid are well mixed with 230 parts by weight of l-phenyl-Z,3-dimethyl-4-isopropyl-5-pyrazolone. The mixture is slightly warmed in an open receptacle on the oil-bath while stirring. When the temperature of the oil has risen to C., the mixture slowly begins to melt. At a temperature of C. in the oil-bath the reaction product represents a clear almost colorless molten mass. It is cooled and soon congeals. The almost colorless compound thus obtained may be easily pulverized. It melts at 126-128" C. By recrystallization from dilute alcohol the melting point rises to 128 C. The compound, which crystallizes in needles, is colorless.

I claim:

1. The compounds of the general formula /CH: 5 CH3 ?=CCH HN-COR GEL-N 00 OH: 1 1/ 0-0 0 I M 05115 HN-CO wherein R represents a saturated or an unsaturated alkyl, R an aryl of the benzene series or a saturated alkyl group, the new compounds being very stable and forming well-shaped crystals, 15 easily soluble in organic solvents, difiicultly soluble in water, and possessing analgesic, antipyretic and soporific properties.

2. The compound of 1-phenyl-2,3-dimethyl-4- isopropyl-S-pyrazolone with isopropyl-allyl-bar- 20 bituric acid, crystallizing in fine colorless needles melting at 128 C., being easily soluble in organic solvents, difiicultly soluble in water and possessing analgesic, antipyretic and soporific properties. 25,

OTTO SCI-INIDER. 

